N-alkylated morphinans are important pharmaceuticals, typically used as analgesics, opiate agonists, and opiate antagonists. With the increasing use of these agents, a practical and effective method of preparation of these compounds is vital to synthesizing diverse N-alkyl substituted morphinans.
Currently, the methods for synthesis of N-alkylated morphinans known in the art have at least one of two primary limitations: (a) their dependence on a transition metal catalyst, and (b) the use of hydrogen gas as a source of hydrogen for the alkylation. Transition metal catalysts are expensive and toxic, which requires testing of the finished product to ensure that the final product does not contain more than a specified parts per million of the transition metal. Additionally, hydrogen gas is hazardous, and methods of synthesis typically employ high pressures. Some prior art methods have incorporated a borohydride to catalyze the reaction. It was desired to avoid this method because the side products are difficult to separate from the desired product, and the reactions may require lower temperatures, −20° to −30° C., when a keto group is present. In light of the current limitations, there is a need for an efficient, cost-effective method of the synthesis of N-alkylated normorphinans.